Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease.

To investigate CSF markers involved in amyloid precursor protein processing, neuronal damage, and neuroinflammation in the preclinical stages of Alzheimer disease (AD) and participants with suspected non-Alzheimer pathology (SNAP). We collected CSF from 266 cognitively normal volunteers participating in a cross-sectional multicenter study (the SIGNAL study) to investigate markers involved in amyloid precursor protein processing (Aβ42, sAPPβ, β-secretase activity), neuronal damage (total-tau [t-tau], phospho-tau [p-tau]), and neuroinflammation (YKL-40). We analyzed the relationship among biomarkers, clinical variables, and the APOE genotype, and compared biomarker levels across the preclinical stages of the National Institute on Aging-Alzheimer's Association classification: stage 0, 1, 2, 3, and SNAP. The median age in the whole cohort was 58.8 years (range 39.8-81.6). Participants in stages 2-3 and SNAP had higher levels of YKL-40 than those in stages 0 and 1. Participants with SNAP had higher levels of sAPPβ than participants in stage 0 and 1. No differences were found between stages 0, 1, and 2-3 in sAPPβ and β-secretase activity in CSF. Age correlated with t-tau, p-tau, and YKL-40. It also correlated with Aβ42, but only in APOE ε4 carriers. Aβ42 correlated positively with t-tau, sAPPβ, and YKL-40 in participants with normal Aβ42. Our findings suggest that inflammation in the CNS increases in normal aging and is intimately related to markers of neurodegeneration in the preclinical stages of AD and SNAP. sAPPβ and β-secretase activity are not useful diagnostic or staging markers in preclinical AD.

Alcolea D ，Martínez-Lage P ，Sánchez-Juan P ，Olazarán J ，Antúnez C ，Izagirre A ，Ecay-Torres M ，Estanga A ，Clerigué M ，Guisasola MC ，Sánchez Ruiz D ，Marín Muñoz J ，Calero M ，Blesa R ，Clarimón J ，Carmona-Iragui M ，Morenas-Rodríguez E ，Rodríguez-Rodríguez E ，Vázquez Higuera JL ，Fortea J ，Lleó A ... -  《-》

Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease.

Alcolea D ，Carmona-Iragui M ，Suárez-Calvet M ，Sánchez-Saudinós MB ，Sala I ，Antón-Aguirre S ，Blesa R ，Clarimón J ，Fortea J ，Lleó A ... -  《-》

Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age.

Sutphen CL ，Jasielec MS ，Shah AR ，Macy EM ，Xiong C ，Vlassenko AG ，Benzinger TL ，Stoops EE ，Vanderstichele HM ，Brix B ，Darby HD ，Vandijck ML ，Ladenson JH ，Morris JC ，Holtzman DM ，Fagan AM ... -  《-》

Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer's disease.

Antonell A ，Mansilla A ，Rami L ，Lladó A ，Iranzo A ，Olives J ，Balasa M ，Sánchez-Valle R ，Molinuevo JL ... -  《-》

Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease.

Lautner R ，Palmqvist S ，Mattsson N ，Andreasson U ，Wallin A ，Pålsson E ，Jakobsson J ，Herukka SK ，Owenius R ，Olsson B ，Hampel H ，Rujescu D ，Ewers M ，Landén M ，Minthon L ，Blennow K ，Zetterberg H ，Hansson O ，Alzheimer’s Disease Neuroimaging Initiative ... -  《-》